The Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) has granted breakthrough therapy designation to the TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; formerly SKB264/MK-2870) plus pembrolizumab (Keytruda) for the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC)with a PD-L1 tumor proportion score (TPS) of at least 1% as well as EGFR- and ALK-negative disease.1
The combination is being examined for the treatment of patients with locally advanced or metastatic NSCLC in the phase 3 OptiTROP-Lung05 trial (NCT06448312). In November 2025, Sichuan Kelun-Biotech Biopharmaceutical Co, the developer of sac-TMT, announced that the study met its primary end point after the combination displayed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs pembrolizumab monotherapy.2 A positive trend in favor of the investigational arm in terms of overall survival (OS) was also reported. In a news release, the company noted that this was the first phase 3 study of an ADC plus an immune checkpoint inhibitor to achieve its primary end point in frontline NSCLC.
Sac-TMT Receives Breakthrough Therapy Designation in China in Frontline NSCLC
- Sac-TMT has been granted breakthrough therapy designation by the Center for Drug Evaluation of China’s National Medical Products Administration in frontline locally advanced/metastatic EGFR- and ALK-negative NSCLC with a PD-L1 TPS of at least 1%.
- The phase 3 OptiTROP-Lung05 trial of sac-TMT plus pembrolizumab met its primary end point of PFS in frontline EGFR- and ALK-negative PD-L1+ NSCLC.
- This was the first phase 3 study of an ADC plus an immune checkpoint inhibitor to achieve its primary end point in frontline NSCLC.
What is the design of OptiTROP-Lung05?
OptiTROP-Lung05 is an ongoing randomized, open-label, multicenter trial that is recruiting patients with PD-L1–positive locally advanced or metastatic NSCLC.3 Eligible patients need to have stage IIIB/IIIC or stage IV disease that is not amenable to radical surgery and/or radical radiotherapy regardless of concurrent chemotherapy, a PD-L1 TPS of at least 1%, at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1 with no worsening within 7 days prior to random assignment, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function. Additionally, patients cannot have received prior systemic anticancer therapy for locally advanced or metastatic disease and must be 18 years to 75 years old.
Patients with an active second malignancy, uncontrolled or clinically significant cardiovascular disease, a history of or current noninfectious pneumonitis/interstitial lung disease, active infection requiring systemic therapy within 2 weeks of random assignment, or active hepatitis B or C viral infection are being excluded from enrollment. Additional exclusion criteria include HIV-positive or a history of acquired immunodeficiency syndrome, a known active syphilis infection, a known allergy to sac-TMT or pembrolizumab, or having undergone major surgery within 4 weeks prior to random assignment or being expected to undergo major surgery during the study.
